Laboratory reporting on the clinical spectrum of CFTR p.Arg117His: Still room for improvement

Nele Laudus; Marie-Pierre Audrézet; Emmanuelle Girodon; Michael A Morris; Dragica Radojkovic; Caroline Raynal; Manuela Seia; Alexandra Štambergová; Heike Torkler; Raina Yamamoto; Elisabeth M C Dequeker

doi:10.1016/j.jcf.2020.05.005

Laboratory reporting on the clinical spectrum of CFTR p.Arg117His: Still room for improvement

J Cyst Fibros. 2020 Nov;19(6):969-974. doi: 10.1016/j.jcf.2020.05.005. Epub 2020 Jun 3.

Authors

Affiliations

¹ Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, University of Leuven, Leuven, Belgium.
² Laboratoire de Génétique Moléculaire, CHU Brest, Brest, France.
³ Laboratoire de Génétique et Biologie Moléculaires, AP-HP.Centre-Université de Paris, Hôpital Cochin, Paris, France.
⁴ SYNLAB Genetics, Lausanne, Switzerland.
⁵ Laboratory for Molecular Biology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
⁶ Laboratoire de Génétique Moléculaire, CHU de Montpellier, Montpellier, France.
⁷ Laboratorio di Genetica Medica - Settore di Genetica Molecolare, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁸ Department of Biology and Medical Genetics, 2nd Faculty of Medicine, Charles University in Prague and Motol University Hospital, Prague, Czech Republic.
⁹ MVZ Dr. Eberhard & Partner Dortmund, Dortmund, Germany.
¹⁰ Biomedical Quality Assurance Research Unit, Department of Public Health and Primary Care, University of Leuven, Leuven, Belgium; Department of Medical Diagnostics, University Hospitals Leuven, Leuven, Belgium. Electronic address: els.dequeker@kuleuven.be.

PMID: 32505523
DOI: 10.1016/j.jcf.2020.05.005

Abstract

Background: The clinical spectrum associated with cystic fibrosis transmembrane conductance regulator (CFTR) variant p.Arg117His is highly variable, ranging from full-blown cystic fibrosis (CF) in a small number of cases to CFTR-related disorders (CFTR-RDs) or no symptoms at all. Therefore, taking into account phenotype variability is essential for interpretation. External quality assessment (EQA) schemes can help laboratories to objectively assess the quality of genotyping and reporting by the laboratory.

Methods: We performed a retrospective longitudinal data analysis on laboratory performance regarding the interpretation of p.Arg117His during CF EQA scheme participation. Completeness and accuracy of reporting on two mock clinical cases were each compared over time (case 1: 2005, 2007 and 2012; case 2: 2015 and 2018). These cases concerned subjects compound heterozygous for p.Phe508del and p.Arg117His in cis with 7T, but with different clinical backgrounds (family planning (case 1) versus diagnostic testing for a child (case 2)). Furthermore, we analyzed the influence of previous participations, annual test volume, accreditation status and laboratory setting on overall performance.

Results: Overall performance improved over time, except during the 2007 CF EQA scheme. In addition, previous participations had a beneficial effect on laboratory performance. Accreditation status, annual test volume and laboratory setting did not significantly influence total interpretation scores.

Conclusions: In general, laboratories performed well on both cases, although reporting on the variable clinical spectrum of p.Arg117His in cis with 7T and on the disease liability of individual CFTR variants can still improve. Moreover, this study underlined the educational role of CF EQA schemes.

Keywords: CFTR-related disorders; Cystic fibrosis; External quality assessment; p.Arg117His.

MeSH terms

Cystic Fibrosis / genetics*
Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
Female
Genetic Predisposition to Disease
Genetic Testing / methods*
Genetic Variation
Genotype
Humans
Longitudinal Studies
Male
Mutation
Phenotype
Retrospective Studies

Substances

Cystic Fibrosis Transmembrane Conductance Regulator